This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This subproject, ongoing for 15 years, addresses the use of MS methods to detect and characterize photodamage to DNA. C to T and CC to TT transition mutations are the most frequent mutations observed in skin cancer. A deamination hypothesis was proposed to address the generation of those mutations. In this hypothesis, a cytosine or 5-methylcytosine photoproduct deaminates to form a uracil or thymine photoproduct. Those uracil or thymine moieties in the photoproduct form Watson-Crick base-pair preferentially with adenine. After two steps of DNA replication, C to T transition mutation results.